{"doi":"10.15252/emmm.202012871","title":"Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers","abstract":"The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulatory factor CFHR1. We further discovered CRTAC1 as a biomarker of alveolar type-2 epithelial cell health status in lavage fluid and plasma. Using cross-modal analysis and machine learning, we identified the cellular source of biomarkers and demonstrated that information transfer between modalities correctly predicts disease status, suggesting feasibility of clinical cell state monitoring through longitudinal sampling of body fluid proteomes.","journal":"EMBO Molecular Medicine","year":2021,"id":4399,"datarank":2.925873784199525,"base_score":4.663439094112067,"endowment":4.663439094112067,"self_citation_contribution":0.6995158641168101,"citation_network_contribution":2.226357920082715,"self_endowment_contribution":0.6995158641168101,"citer_contribution":2.226357920082715,"corpus_percentile":92.5117970140017,"corpus_rank":969,"citation_count":105,"citer_count":77,"citers_with_citation_signal":65,"citers_with_endowment":65,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.648,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-03-02","fair_score":66.6667,"fair_percentile":86.48731274839498,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2925,"name":"Lukas M. Simon","orcid":"0000-0001-6148-8861","position":1,"is_corresponding":false},{"id":2926,"name":"Gabriela Leuschner","orcid":"0000-0002-4717-6922","position":2,"is_corresponding":false},{"id":537,"name":"Meshal Ansari","orcid":"0000-0002-8819-7965","position":3,"is_corresponding":false},{"id":2927,"name":"Philipp E. Geyer","orcid":"0000-0001-7980-4826","position":5,"is_corresponding":false},{"id":540,"name":"Ilias Angelidis","orcid":"0000-0002-0549-8878","position":6,"is_corresponding":false},{"id":538,"name":"Maximilian Strunz","orcid":null,"position":7,"is_corresponding":false},{"id":45213,"name":"Pawandeep Singh","orcid":null,"position":8,"is_corresponding":false},{"id":2929,"name":"Nikolaus Kneidinger","orcid":"0000-0001-7583-0453","position":9,"is_corresponding":false},{"id":2930,"name":"Frank Reichenberger","orcid":null,"position":10,"is_corresponding":false},{"id":2931,"name":"Edith Silbernagel","orcid":null,"position":11,"is_corresponding":false},{"id":2932,"name":"Stephan Böhm","orcid":"0009-0008-4376-9369","position":12,"is_corresponding":false},{"id":2933,"name":"Heiko Adler","orcid":"0000-0002-6481-6709","position":13,"is_corresponding":false},{"id":553,"name":"Michael Lindner","orcid":"0000-0002-2106-0286","position":14,"is_corresponding":false},{"id":45214,"name":"Britta Maurer","orcid":"0000-0001-9385-8097","position":15,"is_corresponding":false},{"id":2934,"name":"Anne Hilgendorff","orcid":"0000-0002-3725-996X","position":16,"is_corresponding":false},{"id":2935,"name":"Antje Prasse","orcid":"0000-0002-7336-7458","position":17,"is_corresponding":false},{"id":33096,"name":"Juergen Behr","orcid":"0000-0002-9151-4829","position":18,"is_corresponding":false},{"id":2937,"name":"Matthias Mann","orcid":"0000-0003-1292-4799","position":19,"is_corresponding":false},{"id":572,"name":"Oliver Eickelberg","orcid":"0000-0001-7170-0360","position":20,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":21,"is_corresponding":false},{"id":573,"name":"Herbert B. Schiller","orcid":"0000-0001-9498-7034","position":22,"is_corresponding":false},{"id":2921,"name":"Janine Gote-Schniering","orcid":"0000-0001-7869-4936","position":23,"is_corresponding":false},{"id":578,"name":"Christoph H. Mayr","orcid":"0000-0001-5353-4768","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"33650774","pmcid":"PMC8033531","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"gold","license":"cc-by","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":83.3333,"fair_a":62.5,"fair_i":20.0,"fair_r":41.6667,"fair_zscore":1.2752,"fair_rationale":{"fair_score":66.67,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":83.33,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"PXD017145","grounded":true,"rationale":"The paper gives PRIDE accession numbers (PXD017145 and PXD017210) which are persistent identifiers in the accepted scheme. 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[majority verdict 'yes' (4/5 passes agreed)]","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Proteome raw data and MaxQuant processing tables can be downloaded from the PRIDE repository under the accession numbers PXD017145 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017145 ) (BALF) and PXD017210 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017210 ) (plasma).","grounded":true,"rationale":"The data-availability statement points to repository records with accessions, which is Colavizza category 3. [majority verdict 'yes' (4/5 passes agreed)]","anchors":["Colavizza, Hrynaszkiewicz, Staden, Whitaker & McGillivray (2020), 'The citation advantage of li","Springer Nature research data policy — Data Availability Statements: standard statement templat","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes"],"scored":false,"signal":null},{"key":"f_discovery_metadata","label":"Description of the dataset as an object","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"We generated subsets of the whole lung parenchyma datasets for COL1A2+ stromal cells (Fig 1C and Appendix Fig S1C–E ), EPCAM+ epithelial cells (Fig 1D and Appendix Fig S1F–H ), CLDN5+ endothelial cells (Fig 1E and Appendix Fig S1I –K), and CD45+ leukocytes (Fig 1F and Appendix Fig S1L–N ).","grounded":true,"rationale":"The dataset content is described in running prose without an itemised inventory such as a section, table, or enumerated list of files or variables. 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[majority verdict 'partial' (4/5 passes agreed)]","anchors":["FORCE11 Joint Declaration of Data Citation Principles (2014) — data should be cited as a first-","RDA-F3-01M — metadata clearly and explicitly includes the identifier of the data it describes","FsF-F3-01M — F-UJI: 'Metadata includes the identifier of the data it describes'"],"scored":true,"signal":null}]},"A":{"name":"Accessible","score":62.5,"criteria":[{"key":"a_data_openly_accessible","label":"Access route free of preconditions","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Proteome raw data and MaxQuant processing tables can be downloaded from the PRIDE repository under the accession numbers PXD017145 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017145 ) (BALF) and PXD017210 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017210 ) (plasma).","grounded":true,"rationale":"The text provides a direct route to download the data via the PRIDE repository without any stated precondition like registration or embargo. [majority verdict 'yes' (4/5 passes agreed)]","anchors":["RDA-A1.1-01D — 'Data is accessible through a free access protocol'","FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","NSTC Desirable Characteristics of Data Repositories (2022) — 'Free and Easy Access'"],"scored":true,"signal":null},{"key":"a_access_conditions_stated","label":"Access level labelled","kind":"llm","weight":1.0,"fraction":0.5,"verdict":"partial","evidence":"Proteome raw data and MaxQuant processing tables can be downloaded from the PRIDE repository under the accession numbers PXD017145 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017145 ) (BALF) and PXD017210 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017210 ) (plasma).","grounded":true,"rationale":"The text describes the action of downloading the data but does not apply an explicit access-level label such as 'open access' or 'freely available'. [majority verdict 'partial' (4/5 passes agreed)]","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The paper involves human-subject data but does not name any gatekeeper, institutional or personal, for data access.","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No sentence in the paper states how long the data will remain available or makes any persistence commitment.","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":20.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format is named for the released data in the text.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No data or metadata community standard (e.g., MIAME, ontology, or checklist) is named as applied to the data.","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"GEO GSE124685","grounded":true,"rationale":"The paper cites at least one identifier for a resource other than its own dataset, such as 'GEO GSE124685' for published bulk RNA-seq data. 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[majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-R1-01M — '(Meta)data are richly described with a plurality of accurate and relevant attribu","FsF-R1-01MD — F-UJI: 'Metadata specifies the content of the data'","NIH DMS Policy Element 3 (NOT-OD-21-014) — Standards (documentation and metadata to accompany t"],"scored":false,"signal":null},{"key":"r_versioning","label":"Snapshot identified","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No version token or date is provided for the released data.","anchors":["DataCite Metadata Schema 4.6 — the 'Version' property","RDA-R1.2-01M — provenance information (which version was used is provenance)","NSTC Desirable Characteristics of Data Repositories (2022) — 'Provenance', 'Retention Policy'"],"scored":true,"signal":null},{"key":"x_code_availability","label":"Analysis code available","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"Count tables of the Munich single‐cell cohort as well as all custom analysis code can be accessed at https://github.com/theislab/2020_Mayr .","grounded":true,"rationale":"The paper provides a GitHub URL as a machine-resolvable locator for the study's own code. 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'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No licence is explicitly attached to the data; the CC BY 4.0 license applies only to the article.","gain":16.67,"priority":"essential","scored":true},{"key":"i_open_nonproprietary_format","dimension":"I","label":"Open file format","action":"Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open proteomics formats such as mzML or mzIdentML.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format is named for the released data in the text.","gain":8.33,"priority":"important","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the proteomics repository accession (e.g. from PRIDE (PXD accession) or ProteomeXchange) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Proteome raw data and MaxQuant processing tables can be downloaded from the PRIDE repository under the accession numbers PXD017145 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017145 ) (BALF) and PXD017210 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017210 ) (plasma).","why":"The dataset identifiers appear only in the body text's data-availability statement, not in the reference list. [majority verdict 'partial' (4/5 passes agreed)]","gain":4.17,"priority":"important","scored":true},{"key":"r_versioning","dimension":"R","label":"Snapshot identified","action":"Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). A reader reproducing your work against 'the current release' is reproducing it against a different dataset.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No version token or date is provided for the released data.","gain":4.17,"priority":"useful","scored":true},{"key":"f_discovery_metadata","dimension":"F","label":"Description of the dataset as an object","action":"Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"We generated subsets of the whole lung parenchyma datasets for COL1A2+ stromal cells (Fig 1C and Appendix Fig S1C–E ), EPCAM+ epithelial cells (Fig 1D and Appendix Fig S1F–H ), CLDN5+ endothelial cells (Fig 1E and Appendix Fig S1I –K), and CD45+ leukocytes (Fig 1F and Appendix Fig S1L–N ).","why":"The dataset content is described in running prose without an itemised inventory such as a section, table, or enumerated list of files or variables. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"a_access_conditions_stated","dimension":"A","label":"Access level labelled","action":"State the access level in words, using the standard vocabulary: 'These data are open access' / 'These data are controlled access'. A reader — and a harvester — should not have to infer the access level from the presence of a download link.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Proteome raw data and MaxQuant processing tables can be downloaded from the PRIDE repository under the accession numbers PXD017145 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017145 ) (BALF) and PXD017210 ( http://www.ebi.ac.uk/pride/archive/projects/PXD017210 ) (plasma).","why":"The text describes the action of downloading the data but does not apply an explicit access-level label such as 'open access' or 'freely available'. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"i_community_standard_vocabulary","dimension":"I","label":"Community standard / vocabulary","action":"Adopt and NAME your domain's data standard — the minimum-information checklist, metadata schema, or ontology your community uses (MIAME/MINSEQE, ISA-Tab, BIDS, an OBO ontology, HL7 FHIR/OMOP) — and say which one you followed. A reporting checklist standardises your paper; it does nothing for your data. In proteomics, describe the data with mzML or MIAPE.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No data or metadata community standard (e.g., MIAME, ontology, or checklist) is named as applied to the data.","gain":0.0,"priority":"important","scored":false},{"key":"r_documentation_codebook","dimension":"R","label":"Documentation / codebook","action":"Ship a README and a data dictionary IN the deposit — every file, every variable, its units, its allowed values, its missing-value codes. It is the cheapest single thing that makes a dataset usable by someone who was not in the lab, and a table buried in the article does not travel with the data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No documentation object (README, data dictionary, codebook) is named as travelling with the deposited data. [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"a_controlled_access_for_sensitive","dimension":"A","label":"Gatekeeper for sensitive data","action":"Route sensitive data through an institutional gatekeeper — deposit in a controlled- access repository (dbGaP, EGA) with a Data Access Committee and a published DUA — rather than through the corresponding author's inbox. An author-gated dataset dies with the author's email address, and 'on reasonable request' has been shown repeatedly not to yield data.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"The paper involves human-subject data but does not name any gatekeeper, institutional or personal, for data access.","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No sentence in the paper states how long the data will remain available or makes any persistence commitment.","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open proteomics formats such as mzML or mzIdentML.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the proteomics repository accession (e.g. from PRIDE (PXD accession) or ProteomeXchange) in the reference list.","Version the deposit and cite the exact version analysed (a version-specific DOI, or an accession with its version suffix). A reader reproducing your work against 'the current release' is reproducing it against a different dataset.","Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. Describe the dataset as an object in its own right, not as a by-product of the findings — this is what makes it discoverable to someone who is not looking for your paper."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T11:03:50.204497Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}